Extensive overlap of mu-opioid and nicotinic sensitivity in cortical interneurons

Cereb Cortex. 2007 Aug;17(8):1948-57. doi: 10.1093/cercor/bhl104. Epub 2006 Oct 26.


We studied mu-opioid transmission in acute slices of rat neocortex using whole-cell recordings and single-cell reverse transcription-polymerase chain reaction. The mu-opioid receptor (MOR) was found in gamma-aminobutyric acidergic (GABAergic) interneurons that were either layer I cells frequently expressing neuropeptide Y or layers II-V cells expressing vasoactive intestinal peptide and enkephalin (Enk). We found that mu-opioid agonists inhibit these interneurons that are selectively excited by nicotinic agonists. The extensive overlap of mu-opioid and nicotinic responsiveness allowed mu-opioid agonists to inhibit nicotinic excitation of responsive interneurons and of their GABAergic output onto pyramidal cells. Finally, nicotinic stimulation resulted in a dynamic sequence where GABAergic transmission was first enhanced and then depressed below its baseline. This latter disinhibitory effect was prevented by a mu-opioid antagonist, indicating that excitation of nicotinic-responsive interneurons induced the release of endogenous Enk, which in turn led to MOR activation. Our results suggest that neocortical mu-opioid transmission acts as an inhibitory feedback onto nicotinic-responsive interneurons, which may change network excitability and inhibition patterns during cholinergic excitation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology*
  • Electrophysiology
  • Enkephalins / biosynthesis
  • Enkephalins / genetics
  • Excitatory Postsynaptic Potentials / drug effects
  • Interneurons / drug effects
  • Interneurons / physiology*
  • Neocortex / drug effects
  • Neocortex / physiology
  • Nerve Net / cytology
  • Nerve Net / physiology
  • Nicotinic Agonists / pharmacology
  • Patch-Clamp Techniques
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Nicotinic / drug effects
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / physiology*
  • Receptors, Opioid, mu / drug effects
  • Receptors, Opioid, mu / genetics
  • Receptors, Opioid, mu / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Synaptic Transmission / genetics
  • Synaptic Transmission / physiology
  • gamma-Aminobutyric Acid / physiology


  • Enkephalins
  • Nicotinic Agonists
  • Potassium Channels
  • Receptors, Nicotinic
  • Receptors, Opioid, mu
  • gamma-Aminobutyric Acid